Fasting-mimicking diet and hormone therapy induce breast cancer regression.

Approximately 75% of all breast cancers express the oestrogen and/or progesterone receptors. Endocrine therapy is usually effective in these hormone-receptor-positive tumours, but primary and acquired resistance limits its long-term benefit1,2. Here we show that in mouse models of hormone-receptor-positive breast cancer, periodic fasting or a fasting-mimicking diet3-5 enhances the activity of the endocrine therapeutics tamoxifen and fulvestrant by lowering circulating IGF1, insulin and leptin and by inhibiting AKT-mTOR signalling via upregulation of EGR1 and PTEN. When fulvestrant is combined with palbociclib (a cyclin-dependent kinase 4/6 inhibitor), adding periodic cycles of a fasting-mimicking diet promotes long-lasting tumour regression and reverts acquired resistance to drug treatment. Moreover, both fasting and a fasting-mimicking diet prevent tamoxifen-induced endometrial hyperplasia. In patients with hormone-receptor-positive breast cancer receiving oestrogen therapy, cycles of a fasting-mimicking diet cause metabolic changes analogous to those observed in mice, including reduced levels of insulin, leptin and IGF1, with the last two remaining low for extended periods. In mice, these long-lasting effects are associated with long-term anti-cancer activity. These results support further clinical studies of a fasting-mimicking diet as an adjuvant to oestrogen therapy in hormone-receptor-positive breast cancer.

Accuracy of Coracoid Bone Graft Placement: Open versus Arthroscopic Latarjet.

Purpose The aim of this study was to compare the accuracy of the coracoid bone graft placement with the open Latarjet-Patte and arthroscopic Latarjet (arthro-Latarjet) procedures in the treatment of anterior instability of the shoulder. Methods Forty-six patients affected by anterior shoulder instability were divided into two groups. In group A ( n = 25), patients were operated by arthroscopic Latarjet (arthro-Latarjet) procedure and in group B ( n = 21), patients were operated by open Latarjet-Patte procedure. Instrumental investigation was based on three-dimensional computed tomography (3D-CT) at a minimum 1-year follow-up. Graft placement and integration, divergence and posterior protrusion of the screws, and glenohumeral osteoarthritis were considered as outcomes. Statistical analysis was performed with chi-square or Fisher's exact test. Significance was set at p < 0.05. Results Positioning of the coracoid graft proved to be optimal in 76% (19/25) of patients of group A and in 100% (21/21) of patients of group B (Fisher's exact test, p = 0.025). Screw placement with respect to the glenoid surface showed a posterior divergence in 44% (11/25) of patients in group A and in 24% (5/21) of patients in group B ( p = 0.15). Posterior protrusion of screw was observed in 76% (19/25) of patients in group A and 71.4% (15/21) of patients in group B ( p = 0.73). Graft integration was present in 76% (19/25) of patients in group A and 85.7% (18/21) of patients in group B (Fisher's exact test, p = 0.48). Mild signs of glenohumeral osteoarthritis were observed in 12% (3/25) of patients in group A and 28.6% (6/21) of patients in group B (Fisher's exact test, p = 0.26). Conclusion Patients operated with open Latarjet-Patte procedure showed better results than those of the arthro-Latarjet group in reference to the positioning of the graft on the coronal plane ( p = 0.025). No significant differences between the groups were observed for graft integration, divergence of the screws, posterior protrusion of the screws, and osteoarthritis. Level of Evidence Level II, nonrandomized prospective comparative study.

Treatment of chronic lateral ankle instability using the Broström-Gould procedure in athletes: long-term results.

PURPOSE: this study was conducted to evaluate long-term results following treatment of chronic lateral ankle instability using the Broström-Gould technique in athletes. METHODS: eighteen athletes involved in competitive sports at different levels, who suffered from chronic lateral ankle instability, underwent Broström-Gould ligamentoplasty between 2000 and 2005. The results of the surgery were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) scale. RESULTS: the results at 10-15 years of follow-up were excellent in 94.5% of these cases and good in the remaining 5.5%. An increase of 31.2 points in the AOFAS scale score was recorded at follow-up (with the score rising to 98.8, from 67.6 preoperatively). All the athletes returned to their respective sports at the same level as prior to the surgery. Imaging at long-term follow-up showed no signs of arthritic degeneration. CONCLUSIONS: the results of this study show that the Broström-Gould technique is an effective procedure for the treatment of chronic lateral ankle instability in the athlete, giving excellent long-term results. LEVEL OF EVIDENCE: therapeutic case series, level IV.

Conservative integrated treatment of adhesive capsulitis of the shoulder.

PURPOSE: the aim of this study was to present the results of a conservative treatment for adhesive capsulitis based on an original protocol of combined pharmacological and rehabilitation treatment. METHODS: fifty-two patients with idiopathic adhesive capsulitis were enrolled in the present study. The treatment protocol included the use of hyaluronic acid and anaesthetic periarticular and intra-articular injections followed by a specific program of capsule and muscle stretching. RESULTS: the results of this treatment showed complete recovery of range of motion (ROM) in 50 of the 52 cases. The mean pre-treatment ROM values were: 85° for forward elevation, 75° for abduction, 25° for external rotation, and 15° for internal rotation. The post-treatment mean ROM values showed marked improvements: 175° for forward elevation, 175° for abduction, 87.5° for external rotation and 75° for internal rotation. CONCLUSIONS: conservative treatment of adhesive capsulitis based on a combined pharmacological and rehabilitation approach was found to be effective in resolving pain and stiffness in 96% of the patients. LEVEL OF EVIDENCE: level IV, therapeutic case series.